Liver disease risk attributable to HCV, HIV, and HCV-HIV coinfection: an interaction analysis

Objective — To quantify whether living with HIV modifies the effect of hepatitis C (HCV) infection on risk of cirrhosis, hepatic decompensation (decompensation), and hepatocellular carcinoma (HCC) in a real-world healthcare context.

Design — A cohort of 1 484 587 individuals from Ontario, Canada that tested negative for HCV antibodies (HCV Ab−) were followed from 1999 to 2018 for diagnoses of HCV, HIV, cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma, using administrative health data.

Methods — Time-dependent Cox regression was used to quantify the risk of each liver disease outcome in individuals who were positive for HCV and HIV (HCV+/HIV+), only HCV+ (HCV+/HIV−), only HIV+ (HCV−/HIV+), and doubly negative (HCV−/HIV−). The relative excess risk due to interaction (RERI) was calculated to quantify the magnitude and significance of interaction effects.

Results — HCV+/HIV+ had the highest risk of cirrhosis [hazard ratio (HR) = 3.8; 95% confidence interval (CI): 2.9, 4.9], decompensation (HR = 2.8; 95% CI: 1.9, 4.1), and HCC (HR = 4.1; 95% CI: 2.7, 6.2) compared to HCV−/HIV−. A significant positive interaction effect was observed for risk of decompensation (RERI = 1.2; 95% CI: 0.1, 2.3) and HCC (RERI = 2.3; 95% CI: 0.6, 4.0), but not for risk of cirrhosis (RERI = 0.9; 95% CI: −0.1, 2.0).

Conclusions — This large population-based cohort study is the first to estimate the interaction effect of HCV and HIV on liver disease risk, providing new evidence of a synergistic additive interaction effect between HCV and HIV infection on risk of decompensation and HCC.